These studies are designed to determine the pathogenesis of the degenerative arthropathies associated with the deposition of calcium pyrophosphate dihydrate or basic calcium phosphate crystals in articular tissues with the eventual goal of developing a rational means of preventing or reversing the consequences of such deposition. This proposal focuses chiefly on the interaction of living cells with crystals containing calcium. We shall examine how the observed biological effects such as stimulation of mitogenesis, crystal dissolution, arachidonic acid metabolism and proteases synthesis are related to each other. We shall further define the mechanism of BCP crystal-induced mitogenesis with special emphasis on early biochemical changes in cells stimulated by crystals. The mechanism of BCP crystal dissolution by cells will be explored. We are interested in possible intracellular sequestration of Ca2+ resulting from crystal dissolution and rate of Ca2+ efflux. Other related studies will include: level of somatomedin C in joint fluids of arthritis patients; 2) clearance of BCP crystals from human joints. Rabbits and mice will be used as a source for cells for cell culture.